Identification of ADAM10 as a major TNF sheddase in ADAM17-deficient fibroblasts

Renata Mezyk-Kopeć; Monika Bzowska; Krystyna Stalińska; Tomasz Chełmicki; Michał Podkalicki; Jarosław Jucha; Katarzyna Kowalczyk; Paweł Mak; Joanna Bereta

doi:10.1016/j.cyto.2009.03.002

Identification of ADAM10 as a major TNF sheddase in ADAM17-deficient fibroblasts

Renata Mezyk-Kopeć, Monika Bzowska, Krystyna Stalińska, Tomasz Chełmicki, Michał Podkalicki, Jarosław Jucha, Katarzyna Kowalczyk, Paweł Mak, Joanna Bereta^*

^*Corresponding author for this work

Jagiellonian University

Research output: Contribution to journal › Article › peer-review

Abstract

ADAM17 (a disintegrin and metalloprotease)-deficient murine fibroblasts stably transfected with proTNF cDNA release significant amounts of biologically active soluble TNF. The enzyme responsible for this activity is a membrane protein that hydrolyzes the peptide bond Ala⁷⁶:Val⁷⁷ within proTNF. Its activity is inhibited by 1,10-phenantroline and GM6001, insusceptible to TIMP-2 (tissue inhibitor of metalloproteinases-2), and stimulated by ionomycin. These characteristics match ADAM10. The moderate silencing of ADAM10 by shRNA resulted in a significant inhibition of TNF shedding. There was no correlation between the level of ADAM10 expression and the presence of active ADAM17. Our results indicate that ADAM10 may function as the TNF sheddase in cells which lack ADAM17 activity.

Original language	English
Pages (from-to)	309-315
Number of pages	7
Journal	Cytokine
Volume	46
Issue number	3
DOIs	https://doi.org/10.1016/j.cyto.2009.03.002
Publication status	Published - Jun 2009

Keywords

ADAM10
ADAM17
Ectodomain shedding
RNA interference
TNF

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

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10.1016/j.cyto.2009.03.002

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@article{02540246d2c04696b7884f41497fa76c,

title = "Identification of ADAM10 as a major TNF sheddase in ADAM17-deficient fibroblasts",

abstract = "ADAM17 (a disintegrin and metalloprotease)-deficient murine fibroblasts stably transfected with proTNF cDNA release significant amounts of biologically active soluble TNF. The enzyme responsible for this activity is a membrane protein that hydrolyzes the peptide bond Ala76:Val77 within proTNF. Its activity is inhibited by 1,10-phenantroline and GM6001, insusceptible to TIMP-2 (tissue inhibitor of metalloproteinases-2), and stimulated by ionomycin. These characteristics match ADAM10. The moderate silencing of ADAM10 by shRNA resulted in a significant inhibition of TNF shedding. There was no correlation between the level of ADAM10 expression and the presence of active ADAM17. Our results indicate that ADAM10 may function as the TNF sheddase in cells which lack ADAM17 activity.",

keywords = "ADAM10, ADAM17, Ectodomain shedding, RNA interference, TNF",

author = "Renata Mezyk-Kope{\'c} and Monika Bzowska and Krystyna Stali{\'n}ska and Tomasz Che{\l}micki and Micha{\l} Podkalicki and Jaros{\l}aw Jucha and Katarzyna Kowalczyk and Pawe{\l} Mak and Joanna Bereta",

year = "2009",

month = jun,

doi = "10.1016/j.cyto.2009.03.002",

language = "English",

volume = "46",

pages = "309--315",

journal = "Cytokine",

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TY - JOUR

T1 - Identification of ADAM10 as a major TNF sheddase in ADAM17-deficient fibroblasts

AU - Mezyk-Kopeć, Renata

AU - Bzowska, Monika

AU - Stalińska, Krystyna

AU - Chełmicki, Tomasz

AU - Podkalicki, Michał

AU - Jucha, Jarosław

AU - Kowalczyk, Katarzyna

AU - Mak, Paweł

AU - Bereta, Joanna

PY - 2009/6

Y1 - 2009/6

N2 - ADAM17 (a disintegrin and metalloprotease)-deficient murine fibroblasts stably transfected with proTNF cDNA release significant amounts of biologically active soluble TNF. The enzyme responsible for this activity is a membrane protein that hydrolyzes the peptide bond Ala76:Val77 within proTNF. Its activity is inhibited by 1,10-phenantroline and GM6001, insusceptible to TIMP-2 (tissue inhibitor of metalloproteinases-2), and stimulated by ionomycin. These characteristics match ADAM10. The moderate silencing of ADAM10 by shRNA resulted in a significant inhibition of TNF shedding. There was no correlation between the level of ADAM10 expression and the presence of active ADAM17. Our results indicate that ADAM10 may function as the TNF sheddase in cells which lack ADAM17 activity.

AB - ADAM17 (a disintegrin and metalloprotease)-deficient murine fibroblasts stably transfected with proTNF cDNA release significant amounts of biologically active soluble TNF. The enzyme responsible for this activity is a membrane protein that hydrolyzes the peptide bond Ala76:Val77 within proTNF. Its activity is inhibited by 1,10-phenantroline and GM6001, insusceptible to TIMP-2 (tissue inhibitor of metalloproteinases-2), and stimulated by ionomycin. These characteristics match ADAM10. The moderate silencing of ADAM10 by shRNA resulted in a significant inhibition of TNF shedding. There was no correlation between the level of ADAM10 expression and the presence of active ADAM17. Our results indicate that ADAM10 may function as the TNF sheddase in cells which lack ADAM17 activity.

KW - ADAM10

KW - ADAM17

KW - Ectodomain shedding

KW - RNA interference

KW - TNF

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U2 - 10.1016/j.cyto.2009.03.002

DO - 10.1016/j.cyto.2009.03.002

M3 - Article

C2 - 19346138

AN - SCOPUS:67349226089

SN - 1043-4666

VL - 46

SP - 309

EP - 315

JO - Cytokine

JF - Cytokine

IS - 3

ER -

Identification of ADAM10 as a major TNF sheddase in ADAM17-deficient fibroblasts

Abstract

Keywords

UN SDGs

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